During the productive infection of KB cells by adenovirus type 5, there is a progressive decrease in the level of cellular DNase III activity. The decrease requires protein synthesis after infection. It does not occur after infection at the non-permissive temperature by Ad5 ts125, a DNA negative mutant which fails to induce the adenovirus-specific DNA binding protein. This is the first example in animal viruses of a viral mechanism for the manipulation of the cellular environment by effects on specific cell enzymes. This mechanism appears to be a common one in bacteriophage infections. The adenovirus-induced inhibition of DNase III will be studied in order to ascertain both its mechanism and its biological role(s). The possible function of the adenovirus DNA binding protein as DNase inhibitor will be examined, as well as the mechanism of inhibition. Possible physiological effects of the inhibition will be studied, including the adenovirus-induced shut-off of host DNA synthesis, adenovirus inhibition of SV40 DNA replication, and permissiveness of cells for different adenovirus serotypes. Several approaches will be used to ascertain the role of DNase III in the cell. The effect of adenovirus infection on another cell enzyme, DNase IV, will also be studied.